If this is for TRS06 or TC, then it sounds like the registry keys that CMP uses to locate Trainz are missing, but running Trainz should have corrected that. I'm not sure if the Content Manager for UTC or TRS04 need the registry keys, but it could be possible.
The best I can recommend is to reinstall Trainz. It may be time-consuming, but reinstalling can solve a lot of problems.
Chris