First, make sure that your cable is plugged into the USB port. Connect the radio to the cable. Turn on the radio and make sure the radio has a freshly charged battery before you ever do any programming are you will turn your radio into a permanent paperweight that looks like a XTS5000 radio.
In CPS, click on the "File" tab, Select "Read" Device, (a Select Port Box will pop up) "USB" should be shown and that should be your only option and to make sure select the pull down and click on "USB" and click "Ok". You should be good to GO and you shouldn't have to do it again for that codeplug file and you shouldn't have to do that procedure for another codeplug file. Just remember that procedure just in case.
After you select the USB in the Port setting and click "Ok", it should be reading the radio and you should have gotten a confirmation Tone/Beep, you should see the progress of the read action in the lower left corner in the CPS and the radio display will show you "Program Mode", watch the progress status and it should show about three different progress actions with the last one being "Validating Data' and the after the validating, the CPS should be launched. After the CPS is launched, save your codeplug file and name it "master" codeplug file. Then do a "Save As" and call the file with another name and work with that file from now on. The Master Codeplug File will be your backup file in case you do something wrong with your working file. Always, after you read or write, just make sure that the radio has completely Reset before you turn off the radio and disconnect the programming cable so you don't corrupt the codeplug with a fatal error.