Fine, well, if you look at a map of America(go on Google Maps or something) and you draw a line from D.C., to Cleveland Ohio, to Nashville Tennessee, to Atlanta Georgia, back to D.C., you will end up with a box.
Inside this box is a fairly large portion of America that lacks any real major metropolitan areas, and consists mostly of small towns.
Given what we saw/heard about states like Utah, Arizona, New Mexico, and Colorado, its very likely that, shortly after the war, the people in this area who didn't die from all the radiation would have quickly run out of supplies, since their small towns aren't self sustaining, and the remaining people would have been forced to either
A. Move to the ruins of the major metropolis areas around the boxed area.
B. Degenerate into tribal groups like those seen in places like Zion.
C. Go sort of Point Lookout natives, and establish very small self sustaining communities.
While this wouldn't have caused the area to be totally abandoned, there basically wouldn't be any significant number of people in it to maintain any sort of actual civilization, thus resulting in the area turning into mostly hostile wilderness.
This in turn would have basically made east/west travel impossible, as this boxed area extended from the Great Lakes, down to Georgia in the south. Realistically, the only "safe" ways west would be to either
A. Go through Pittsburgh(which we all know how big of a dump that was), into Ohio, and then go west to places like Chicago.
B. Go all the way south from D.C., through the Carolinas, and into Atlanta, and then start going west to Dallas and beyond.
And neither of these paths are very efficient to travel.
This is somewhat supported in Fo3 and its DLC, where we hear of settlements all along the coast, from Boston down to The Broken Banks, but we hear nothing of anything in more nearby places like West Virginia, Western Virgina, and everything else in the boxed area.
Basically, this entire interior area of America is wilderness.