Since I'm around Brian's age and have family in Columbus, this case sticks with me more than most. Since there's been no conclusive evidence, I figured it can't hurt to explore all possibilities (no matter how unlikely).
Again, I emphasize (like I did above) that I'm a rational individual. I fully understand it's most likely he had an unfavorable accident or encounter while moving around downtown alone at night, under the influence.
So this is--admittedly--wishful thinking, I know, but since Clint's lawyer seems to have suggested Brian may have left on his own accord, I'm trying to think of what possibilities that could've prompted Brian to leave.
1. Obviously, it's been mentioned that Brian may have been disaffected/depressed/traumatized by the stress of school and the loss of his mother. That this deep disillusionment could've motivated him to somehow flee a society that had disappointed him. While that's not unheard of, it sure doesn't happen often...especially this permanently. But here's an additional question: Is there any chance Brian would be discouraged from returning because he would face some sort of legal charges or overwhelming debt if he came back? Does he have monstrous student loans? Would leaving the program without notice--especially if funded by some sort of scholarship--be considered "stealing" from the donor in a sense?
2. I saw someone suggest he may have entered the Witness Protection Program back a ways in this thread. To me it seems really far-fetched that anything occurred that night which instantly qualified him for such a program. But is there any chance he witnessed something prior to that night and knew he would be entering the program for the safety of his family? Again, this seems highly unlikely given that he probably spent most of his time surrounded by medical professionals and not on the streets, but I'll mention it since I saw someone else optimistically suggest it.
3. I need some help thinking about this one. Could Brian have been being recruited into something? A health organization that works in the developing world? An elite branch of the military? Some sort of undercover operation? (I know this is starting to sound like a movie, but since it's been so long, I just wondered if anyone could think of any possibilities like this that are even in the realm of feasible.) This is a very smart, tall, strong educated man. It seems reasonable there could've been people trying to recruit him into elite fields or work. Is there any chance Clint knew of interactions like this? Of Brian considering certain unusual lines of work? Again, not by far the most likely explanation. The only reason I'm even able to entertain it--for a minute--is that Clint (if truthful) seems to think Brian chose to leave. Also, Brian did go out for "one last night with his friends" and unequivocally told his girlfriend he loved her in his parting message. He also had dinner with his dad that night and talked to his brother and invited him to hangout too. Was he trying to say a last goodbye to everyone? Or, did he know something was going to happen that night? Is that why even though Clint took Meredith, he didn't take Alexis?