According to the developer documentation on Apple's website: https://developer.apple.com/library/ios/#qa/qa1719/_index.html
Starting in iOS 5.0.1 a new "do not back up" file attribute has been introduced allowing developers to clearly specify which files should be backed up. (com.apple.MobileBackup)
Persistance is easily achievable (LocalFileSystem.PERSISTENT) but there seems to be no way of specifying if a saved file is not backed up to the iCloud or not.
Apps may be rejected by Apple (depending on the data) if the "do not back up" file attribute is not set.